Protective effects of amylin on reserpine-induced gastric damage in the rat.

Here we show that the vasoactive peptide amylin protects against reserpine-induced gastric injury in the rat, resulting in lower score of gastric lesions. Hepatocyte growth factor (HGF), its c-Met receptor and cyclooxygenase-2 (COX-2) expression, usually increased in course of reserpine-induced gastric damage, was decreased in rats treated with amylin. Pretreatment with the specific amylin receptor antagonist AC187 abrogated the gastroprotective effects of amylin and restored high expression levels of HGF, c-Met and COX-2.

Adrenomedullin modulates COX-2 and HGF expression in reserpine-injuried gastric mucosa in the rat.

Here we show the increased hepatocyte growth factor (HGF) and cyclooxygenase-2 (COX-2) expression in gastric mucosa of rats which have developed a reserpine-induced ulcer. Such an increase of HGF and COX-2 expression was blunted in rats pretreated with adrenomedullin. Pretreatment with adrenomedullin and the adrenomedullin22-52 fragment did not result in changes of HGF and COX-2 expression, compared to the reserpine and adrenomedullin treated group.

Effect of adrenomedullin on c-Met receptor expression after reserpine-induced gastric damage in the rat.

Here, we show an increase in c-Met receptor expression during reserpine-induced gastric damage in the rat, as assessed by immunohistochemistry. Pretreatment of animals with adrenomedullin prevented this increase in c-Met expression. c-Met immunoreactivity was localized in gastric glands.

Secretory and vascular effects of adrenomedullin in gastric ulcer: role of CGRP- and adrenomedullin-receptors.

Adrenomedullin prevents damage of gastric mucosa in either reserpine-treated or pylorus-ligated rats. Pre-treatment with CGRP(8-37) resulted in a decrease of the gastro-protective effect of adrenomedullin in both models and reversed the inhibitory effect of adrenomedullin on gastric acid output in the pylorus-ligated rats. These adrenomedullin actions were less effectively modified by pre-treatment with adrenomedullin(22-52).

Effects of adrenomedullin on the contraction of gastric arteries during reserpine-induced gastric ulcer.

Adrenomedullin (100 ng/kg, s.c.) prevents reserpine-induced damage of gastric mucosa.

Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta.

1 We investigated the effects of prolonged exposure to copper (Cu(2+)) on vascular functioning of isolated rat aorta. 2 Aortic rings were exposed to CuSO(4) (3-24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu(2+). 3 Exposure to 2 micro M Cu(2+) in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h.

Gastroprotective effect of adrenomedullin administered subcutaneously in the rat.

Subcutaneous injections of adrenomedullin prevented reserpine-induced gastric mucosal damage in a dose-dependent manner (1-1000 ng/kg), but did not interfere with the lesions produced by ethanol administration. In pylorus-ligated rats adrenomedullin significantly reduced gastric volume, total and free acid output as well as ulcer formation. The gastroprotective activity of adrenomedullin was not present in rats pretreated with cysteamine.

Grapefruit juice effects on the bioavailability of cyclosporin-A in rats.

Previous studies indicate that blood levels of cyclosporin-A are increased by concomittant administration of grapefruit juice in healthy subjects and patients. It was suggested that grapefruit juice could inhibit the metabolism of cyclosporin-A by CYP3A4, the predominant cytochrome P450 enzyme in the gut wall and liver. However, up to date, the mechanism of action of grapefruit juice has not been conclusively identified and no work has been conducted in animals to quantify its effect on cyclosporin-A metabolism.

Role of soy diet and L-arginine in cyclosporin-A-induced osteopenia in rats.

Our previous studies show that chronic administration of L-arginine decreases cyclosporin-A-induced bone loss. The present study was designed to investigate whether a soy diet could prevent cyclosporin A-induced osteopenia and eventually improve the protective effect of L-arginine. Rats on soy diet were treated with cyclosporin-A, L-arginine, cyclosporin-A + L-arginine or saline.

Responsiveness of irradiated rat anterior pituitary cells to hypothalamic releasing hormones is restored by treatment with growth hormone.

Hypopituitarism is a common sequela of irradiation in cancer patients. Here we report that recombinant human growth hormone (r-hGH) prevents cell death and restores secretory capacity of irradiated rat pituitary cells in vitro. Dispersed rat pituitary cells from male Sprague-Dawley rats, irradiated with a 9-Gy sublethal dose, were incubated with r-hGH before, after, or before and after irradiation.

Antiinflammatory activity of adrenomedullin in the acetic acid peritonitis in rats.

The antiinflammatory effect of ADM was studied in different models of inflammation and compared to the one of CGRP. Peptides were active against acetic acid-induced peritonitis in the rats. ADM and CGRP exerted the antiinflammatory effect at different doses, 400 and 20 ng/kg respectively, but with different efficacy (ADM >CGRP).

Effects of centrally of peripherally injected adrenomedullin on reserpine-induced gastric lesions.

Adrenomedullin intracerebroventricularly administered (0.1 to 20 ng/rat i.c.

Involvement of DA1 and DA2 receptors in the gastroprotective activity of amylin in the rat.

Peripheral administration of amylin (40 microg kg-1) exerts gastroprotective effects in the reserpine-induced gastric lesions in the rat. This activity is decreased by pretreatment (30 min before) with (-)-sulpiride (0.1 mg kg-1 s.

Synthesis and pharmacological evaluation of 1-methyl-5-[substituted-4 (3H)-oxo-1,2,3-benzotriazin-3-yl]-1H-pyrazole-4-acetic acid derivatives.

Several new 1-methyl-5-[substituted-4-oxo-1,2,3-benzotriazin-3-yl] -1H-pyrazole-4-acetic acids and their ethyl ester derivatives were prepared. The compounds were tested for analgesic and antiinflammatory activities, acute toxicity, ulcerogenic effect, and as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), since it is claimed that the inhibition of such an enzyme predicts in vivo antiinflammatory activity. Some compounds were more active than phenylbutazone in the phenylbenzoquinone and acetic acid peritonitis tests, and equiactive to the same drug in the carrageenin paw edema test.

Synthesis of new thieno [2,3-d]pyrimidine-2,4(1H,3H)-diones with analgesic and anti-inflammatory activities.

A series of new 1,3-disubstituted thieno[1,3-d]pyrimidine-2,4(1H,3H)-diones were prepared to investigate their analgesic and anti-inflammatory properties. The analgesic and anti-inflammatory activities of synthesized compounds were investigated by the phenylquinone-induced writhing syndrome test, carrageenan rat paw oedema test and acetic acid-induced peritonitis assay. Most of the new compounds were found to be superior to mefenamic acid, as they were devoid of any ulcerogenic activity.

L-propionyl carnitine, an endogenous ester in fatty acid metabolism, exerts anti-shock and endothelial protective effects in rat splanchnic ischemia-reperfusion injury.

Splanchnic artery occlusion (SAO) results in a severe form of circulatory shock in which oxygen-derived free radicals play an important role. L-Propionyl carnitine (LPC), an endogenous ester that plays a crucial role in cellular fatty acid oxidation and metabolism, has been shown to exert a protective effect in myocardial ischemia/reperfusion injury. Our purpose was to investigate the effects of LPC in an SAO model of ischemia/reperfusion injury.

Effect of amylin in various experimental models of gastric ulcer.

Subcutaneous administration of amylin (20-40 micrograms/kg) prevented, in a dose-dependent manner, reserpine- and serotonin-induced gastric damage, but the anti-ulcer effect was not present when lesions were induced by pylorus ligation. The protective effect of amylin was inhibited by pretreatment with capsicin as well as CGRP-(8-37), a calcitonin gene-related peptide (CGRP) and amylin receptor antagonist, and was significantly reduced by domperidone, a dopamine D2 receptor antagonist, or neostigmine, an inhibitor of acetylcholinesterase. Our data suggest that the gastroprotective activity of amylin in some experimental models of gastric ulcers involves capsaicin-sensitive fibers and CGRP receptors.

Protective action of epidermal growth factor and a fraction from Triticum vulgare extract in mouse tail necrosis.

Several peptide growth factors, including EGF, are known to protect endothelium from oxygen-related damage or ischemia-reperfusion, in vitro experiments show that such protective effect involves endogenous endothelium-related factors like nitric oxide and prostanoids. However, in vivo demonstrations of a possible role in related vascular diseases are lacking. In our experiments, human EGF and fraction C, a 3-10 kDa oligosaccharidic fraction from an aqueous extract of Triticum vulgare, known as growth promoters for several cell types including endothelial cells, were found protective against ischemic necrosis of the mouse tail induced by i.

Amylin given by central or peripheral routes decreases gastric emptying and intestinal transit in the rat.

The effect of rat amylin on gastric emptying and intestinal transit in the rat was examined. Amylin administered intracerebroventricularly (1, 2, 2.5 or 4 micrograms/rat) produced the maximal decrease in gastric emptying and intestinal transit at the dose of 2.

Protective effect of propionyl-L-carnitine against PAF-induced rat paw oedema.

Recent reports from our laboratory gave evidence showing that propionyl-L-carnitine (PLC), unlike L-carnitine (LC) and acetyl-L-carnitine (ALC), has anti-inflammatory activity in some models of vascular inflammation in rodents. The present paper shows that PLC (50 to 200 mg kg-1 i.p.

Anti-inflammatory activity of amylin and CGRP in different experimental models of inflammation.

The anti-inflammatory activity of amylin was studied in different models of inflammation, and compared to that of CGRP. Both peptides were active against mouse ear oedema induced by croton oil and acetic acid-induced peritonitis in the rat. CGRP was more potent than amylin in both models.

Toxicological evaluation of pidotimod.

This paper reports the toxicological evaluation of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6). Its acute toxicity in mice, rats and dogs was very low after oral, i.v.

Synthesis and pharmacological properties of benzothiazole, 1,3-4-oxadiazole and 1,3,4-thiadiazole derivatives.

The reaction of the 2-amino-substituted 1,3,4-oxadiazoles 9, 10 and the benzothiazoles 11, 12 with ethyl cyanoacetate is described. The obtained cyanoacetamide derivatives 13-16 gave the benzylidene derivatives 18-21 by condensation with benzaldehyde. 2-Phenyl-5-amino-1,3,4-oxadiazolo[3,2-a]pyrimidin-7-one (17) was also obtained.

Protective effects of papaverine salicylate in mouse ear dermatitis and PAF-induced rat paw oedema.

Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine.

A role for nitric oxide in the anti-ulcer activity of calcitonin gene-related peptide.

The anti-ulcer activity of calcitonin gene-related peptide (CGRP) was inhibited, in a dose-dependent manner, by pretreatment with NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Our results suggest that endogenous nitric oxide is involved in the anti-ulcer activity of CGRP.